Silver Nanoparticles from Arbutus Unedo Extract: Green Synthesis, Antibacterial Activity, and TMPRSS2 Enzyme Inhibition

Abstract

This study examines the green synthesis and characterization of silver nanoparticles (AgNPs) derived from extracts of Arbutus unedo leaves (AUL) and fruits (AUF), with a specific emphasis on their inhibitory effects on Transmembrane Serine Protease 2 (TMPRSS2), an enzyme that facilitates viral entry, including SARS-CoV-2. The phenolic composition of the extracts was analyzed via high-performance liquid chromatography (HPLC). AgNPs were characterized using ultraviolet–visible (UV–Vis) spectroscopy, dynamic light scattering (DLS), Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM). AgNPs displayed a face-centered cubic (fcc) crystalline structure with grain sizes of ∼13.21 nm for AUL_AgNPs and 14.85 nm for AUF_AgNPs. Antibacterial activity was evaluated against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The inhibition zones for E. coli were 23.41 mm and 20.70 mm, for S. aureus, 23.70 mm, and 21.68 mm for AUF_AgNPs and AUL_AgNPs, respectively. Cytotoxicity was assessed using direct and indirect XTT assays on L929 fibroblast cells. AUL_AgNPs and AUF_AgNPs showed high viability (∼125% and 120%) at 100 μg/mL in direct contact, with extracts around 100%, indicating low toxicity. In indirect assays, viability decreased with dose, with AUL_AgNPs at ∼80% and AUF_AgNPs at ∼65% at 100 μg/mL. TMPRSS2 inhibition assays demonstrated that AUL_AgNPs achieved approximately 69% inhibition at 100 μg/mL. Although the AgNPs were less effective than the reference inhibitor Camostat (50 nM), they exhibited non-covalent interactions with TMPRSS2. This suggests their potential as multifunctional therapeutic agents with antimicrobial and enzyme-inhibitory activity. © 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.